title: Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis.
abstract: OBJECTIVE
  Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Genetic factors are critical in determining susceptibility to PBC. Among human leuocyte antigen (HLA) genes, an association between the DRB1*08 allele and PBC has been reported in many populations, but not in Chinese patients.
  
  
  METHODS
  We investigated HLA-A, B, DRB1, and DQB1 alleles and haplotypes in 145 PBC patients and 500 healthy subjects. Patients were also stratified according to autoantibody features, and associations between these and HLA alleles were analyzed.
  
  
  RESULTS
  Significant associations existed between HLA-DRB1*08:03 (22.1% vs. 9.0%, Pc < 0.0001, OR = 2.86), DQ2 (41.4% vs. 25.4%, Pc < 0.0001, OR = 2.07) and DQB1*06:01 (31.0% vs. 17.8%, Pc = 0.014, OR = 2.08) alleles and PBC. DRB1*08:03-DQB1*06:01 (22.1% vs. 8.2%, P < 0.0001, OR = 3.17) and DRB1*07:01-DQB1*02:02 haplotypes (28.3% vs. 17.6%, P = 0.005, OR = 1.85) were also associated with PBC susceptibility. In contrast, the DQB1*03:01 allele (21.4% vs. 39.2%, Pc < 0.0001, OR = 0.42) and DRB1*12:02-DQB1*03:01 haplotype (6.9% vs. 14.6%, P = 0.015, OR = 0.43) were significantly decreased in PBC patients compared with controls. DRB1*14:54 and DQ5(1) protected against antinuclear antibody (ANA) (OR = 0.25) and anti-gp210 antibody (OR = 0.39) production, respectively, while HLA-B*44:03 predisposed patients to anti-gp210 antibody (OR = 5.70) production.
  
  
  CONCLUSIONS
  These results suggest that Chinese patients with PBC have a distinct genetic background in eastern Asia, and we confirmed the role of HLA genes in determining PBC susceptibility and autoantibody features in the Chinese population.
authors.affiliation: Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors.forename: Dan-Tong
authors.initials: DT
authors.lastname: Zhao
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Liao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Zhang
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Sun
authors.forename: Yin-Xue
authors.initials: YX
authors.lastname: Ma
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D044466:Asian People; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics* / Q000378:metabolism; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio
chemical_list: D000974:Antibodies, Antinuclear; D015234:HLA-A Antigens; D059866:HLA-DQ beta-Chains; D059811:HLA-DRB1 Chains
keywords: anti-gp210 antibody; antinuclear antibody; genetic susceptibility; human leucocyte antigen; primary biliary cirrhosis